A5067993987- Cell death mechanisms and regulation
- Autophagy in Disease and Therapy
- Neuropeptides and Animal Physiology
- Neurofibromatosis and Schwannoma Cases
- Mitochondrial Function and Pathology
- Neuroblastoma Research and Treatments
- Receptor Mechanisms and Signaling
- Cancer-related Molecular Pathways
- Digestive system and related health
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- RNA Interference and Gene Delivery
- Pain Mechanisms and Treatments
- Neuroendocrine regulation and behavior
- Adversarial Robustness in Machine Learning
- Neurogenesis and neuroplasticity mechanisms
- Glioma Diagnosis and Treatment
- MicroRNA in disease regulation
- Nerve injury and regeneration
- Stress Responses and Cortisol
- Gaussian Processes and Bayesian Inference
- Neuroendocrine Tumor Research Advances
- Anesthesia and Neurotoxicity Research
- Lysosomal Storage Disorders Research
- Helicobacter pylori-related gastroenterology studies
Columbia University
2015-2023
ETH Zurich
2017-2021
Columbia University Irving Medical Center
2016-2021
University of Dundee
2016-2021
Ninewells Hospital
2021
University of Alabama at Birmingham
2008-2017
Board of the Swiss Federal Institutes of Technology
2017
Columbia College
2017
Royal College of Physicians
2017
City College of New York
2017
Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, caspase-activated form of a “BH3-domain–only” BCL-2 family member, triggers homooligomerization “multidomain” conserved proapoptotic members BAK or BAX, resulting release cytochrome c from mitochondria. We find that cells lacking both Bax and Bak , but not only one these components, are completely resistant to tBID-induced apoptosis....
Helicobacter pylori is associated with development of gastritis, gastric ulcers, and adenocarcinomas in humans. The Lewis b (Le ) blood group antigen mediates H. attachment to human mucosa. Soluble glycoproteins presenting the Le or antibodies inhibited bacterial binding. Gastric tissue lacking expression did not bind . Bacteria substituted a terminal GalNAcα1-3 residue (blood A determinant), suggesting that availability receptors might be reduced individuals B phenotypes, as compared O individuals.
bcl-x is a member of the bcl-2 gene family, which may regulate programmed cell death. Mice were generated that lacked Bcl-x. The Bcl-x-deficient mice died around embryonic day 13. Extensive apoptotic death was evident in postmitotic immature neurons developing brain, spinal cord, and dorsal root ganglia. Hematopoietic cells liver also apoptotic. Analyses double-knockout chimeric showed maturation lymphocytes diminished. life-span lymphocytes, but not mature shortened. Thus, Bcl-x functions...
The cytosolic protein APAF1, human homolog of C. elegans CED-4, participates in the CASPASE 9 (CASP9)-dependent activation CASP3 general apoptotic pathway. We have generated by gene trap a null allele murine Apaf1. Homozygous mutants die at embryonic day 16.5. Their phenotype includes severe craniofacial malformations, brain overgrowth, persistence interdigital webs, and dramatic alterations lens retina. fibroblasts exhibit reduced response to various stimuli. In situ immunodetection shows...
The proapoptotic protein BAX contains a single predicted transmembrane domain at its COOH terminus. In unstimulated cells, is located in the cytosol and peripheral association with intracellular membranes including mitochondria, but inserts into mitochondrial after death signal. This failure to insert membrane absence of signal correlates repression signal-anchor function by NH2-terminal domain. Targeting can be instated deleting or replacing segment that BCL-2. stimulated contribution NH2...
Deep generative models based on Generative Adversarial Networks (GANs) have demonstrated impressive sample quality but in order to work they require a careful choice of architecture, parameter initialization, and selection hyper-parameters. This fragility is part due dimensional mismatch or non-overlapping support between the model distribution data distribution, causing their density ratio associated f-divergence be undefined. We overcome this fundamental limitation propose new...
Deep generative models based on Generative Adversarial Networks (GANs) have demonstrated impressive sample quality but in order to work they require a careful choice of architecture, parameter initialization, and selection hyper-parameters. This fragility is part due dimensional mismatch or non-overlapping support between the model distribution data distribution, causing their density ratio associated f -divergence be undefined. We overcome this fundamental limitation propose new...
We disrupted the Mcl-1 locus in murine ES cells to determine developmental roles of this Bcl-2 family member. Deletion resulted peri-implantation embryonic lethality. −/− embryos do not implant utero, but could be recovered at E3.5–4.0. Null blastocysts failed hatch or attach vitro, indicating a trophectoderm defect, although inner cell mass grow culture. Of note, showed no evidence increased apoptosis, exhibited delay maturation beyond precompaction stage. This model indicates that is...
BCL-2-deficient T cells demonstrate accelerated cell cycle progression and increased apoptosis following activation. Increasing the levels of BCL-2 retarded G0-->S transition, sustained cyclin-dependent kinase inhibitor p27Kip1, repressed postactivation death. Proximal signal transduction events immediate early gene transcription were unaffected. However, synthesis interleukin 2 other delayed cytokines markedly attenuated by BCL-2. In contrast, a cysteine protease that also blocks had no...
Min is a fully penetrant dominant mutation that leads to the development of multiple intestinal adenomas throughout duodenal-to-colonic axis. Min/+ C57BL6/J mice have an average life-span 120 d. Multi-label immunocytochemical studies these lesions demonstrate patches differentiated enterocytes, and scattered enteroendocrine, goblet Paneth cells. Expression endogenous marker genes within cells can be directly correlated with position occupied by adenoma along axis mirrors regional...
Helicobacter pylori is a microaerophilic bacterium found in the stomach of asymptomatic humans as well patients with acid peptic disease and gastric adenocarcinoma. We have developed an situ adherence assay to examine cell lineage-specific nature binding this organism characterize surface receptors that recognize its adhesin. Fluorescein isothiocyanate-labeled H. strains were bound mucous cells present pit region human rat units but not neck, parietal, or chief lineages glandular domains...
Abstract α-synuclein (α-syn) is a main component of Lewy bodies (LB) that occur in many neurodegenerative diseases, including Parkinson's disease (PD), dementia with LB (DLB) and multi-system atrophy. α-syn mutations or amplifications are responsible for subset autosomal dominant familial PD cases, overexpression causes neurodegeneration motor disturbances animals. To investigate mechanisms accumulation toxicity, we studied mouse model lysosomal enzyme cathepsin D (CD) deficiency, found...
Glioblastoma (GBM) is a high-grade central nervous system malignancy and despite aggressive treatment strategies, GBM patients have median survival time of just 1 year. Chloroquine (CQ), an antimalarial lysosomotropic agent, has been identified as potential adjuvant in the regimen GBMs. However, mechanism CQ-induced tumor cell death poorly defined. We others shown that CQ-mediated may be p53-dependent at least part due to intrinsic apoptotic pathway. Here, we investigated effects CQ on 5...
Monoclonal antibodies (MAbs) capable of recognizing developmental stage-specific neuronal epitopes are becoming increasingly available. Because most these MAbs raised in a single species (mouse), simultaneous immunofluorescent detection multiple has been difficult. We have taken advantage the high sensitivity tyramide signal amplification to develop protocol that permits two same species. One primary antibody was applied at concentration below limit fluorescently labeled secondary...
Although 1p/19q codeletions define "genetically favorable" oligodendrogliomas, eventual tumor progression and patient death remain constant. Genetic testing is often performed at the time of recurrence, though it unclear whether these or other genetic alterations provide useful prognostic information. We characterized 138 189 (73%) available primary recurrent oligodendroglial neoplasms from 80 patients, utilizing paired FISH probes for 1p32/1q42, 19p13/19q13, CEP7/ EGFR, CEP9/p16,...